Periarterial application of papaverine during laparoscopic donor nephrectomy improves early graft function after kidney transplantation in pigs

Background: Laparoscopic donor nephrectomy (LDN) increases incentives to donation by subjects who might refuse an open operation. However, the incidence of delayed graft function is higher after LDN than after open operation. This may be caused by the reduction of renal perfusion as a result of the raised intraabdominal pressure and mechanically induced renal angiospasm during the operation. We conducted experiments to find out whether the application of papaverine around the renal artery during LDN could improve early graft function after transplantation. Methods: Renal function was studied in 10 male pigs (weight ~25 kg). The left kidney was harvested laparoscopically (intraabdominal pressure 8 mmHg). Five animals were randomly selected to have perivascular application of 50 mg papaverine (treatment group) before preparation of the vessels. In controls no papaverine was used. After LDN and open right nephrectomy the left kidney was autotransplanted. The main outcome measures were volume of urine produced and creatinine clearance during the first 20 h after the transplant. Results: The groups were comparable in respect of body weight, hemodynamic values, amount of infusions, warm and cold ischemia time, and duration of anastomosis. Urine output and creatinine clearance were significantly higher in pigs treated with papaverine than in controls. Conclusions: Papaverine substantially improved early graft function in pigs when applied around the renal artery during LDN. Whether this is applicable to procurement of human kidneys remains to be evaluated. Presented at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons (SAGES) and IPEG, Los Angeles, CA, USA, 10–15 March 2003     

Periarterial papaverine application improves intraoperative kidney function during laparoscopic donor nephrectomy

BACKGROUND: Laparoscopic donor nephrectomy decreases disincentives to donation frequently associated with the disadvantages of open surgery. However, concerns have been raised regarding graft quality, since the incidence of delayed graft function is higher when compared with open procedures. This may be caused by amelioration of kidney perfusion due to the elevated intraabdominal pressure and to a mechanically induced renal angiospasm during donation. This study was addressed to reveal whether the renal periarterial application of papaverine is able to enhance renal blood flow during laparoscopic nephrectomy. MATERIALS AND METHODS: Twelve male piglets underwent left laparoscopic donor nephrectomy after endoscopic occlusion of the right renal vessels and ureter. Urine output and creatinine clearance were determined as indicators of renal blood flow. In the treatment group (n = 6) papaverine hydrochloride was administered to the tissue surrounding the renal artery prior to preparation of the vessels and results were compared with those of controls (n = 6). Free sodium excretion was measured to preclude prerenal failure. RESULTS: In the control group the mean urine output was 0.015 ml/min/kg and the mean creatinine clearance was 0.95 ml/min/kg. In pigs treated with papaverine the mean urine output was 0.052 ml/min/kg and the mean creatinine clearance was 2.22 ml/min/kg. The differences were significant (urine output, P = 0.02; creatinine clearance, P = 0.038). CONCLUSIONS: Papaverine improves renal function during laparoscopic kidney harvest when applied in the vicinity of the renal artery prior to vascular preparation.     

The impact of introducing laparoscopic donor nephrectomy to an established renal transplant program

Background Although the advent of hand-assisted laparoscopic donor nephrectomy (HLDN) has had a positive impact on the donor pool, there is still some concern about its safety. The aim of this study was to assess the impact of a change in surgical access to live-donor nephrectomy on donor-related complication rates, the renal function of the donor, and the graft function of the recipient.Methods At our hospital, HLDN was introduced in 1998. Thereafter, we compared 49 consecutive donors undergoing open donor nephrectomy (ODN) between 1987 and 2002 with 57 consecutive donors undergoing HLDN between 1998 and 2002. Donor renal and recipient graft functions were assessed by measuring creatinine levels and urine output, with the addition of warm and cold ischemia time and dialysis requirements in the latter group. Data are presented as means (±SD) and analyzed with the Student t-test or Fishers exact test.Results The ODN and HLDN donors were comparable for age, gender, body mass index, renovascular anatomy, and preoperative creatinine. Estimated blood loss (370 ± 280 vs 168 ± 160 ml, p < 0.0001), time to resumption of oral intake (1.7 ± 0.5 vs 1.3 ± 0.7 days, p = 0.01), duration of intravenous narcotic requirements (23 ± 0.7 vs 1.7 ± 1.0 days, p < 0.0001), and hospital stay (4.2 ± 1.4 vs 2.9 ± 1.3 days, p < 0.0001) were significantly decreased after HLDN. There were no significant differences between ODN and HLDN in operating time (204 ± 46 vs 202 ± 49 min), donor-related complication rates (12.2% vs 14%), or donor renal and recipient graft functions.Conclusion The introduction of HLDN to an established renal transplant program led to an improved short-term outcome without any increase in donor-related complication rates or delay in recipient graft function.     

Renal hemodynamic response to ureteral obstruction during converting enzyme inhibition

Acute unilateral obstruction (UUO) of the pig kidney is associated with an increased secretion of intrarenally generated angiotensin II (ANG II). In order to clarify the importance of this intrarenal ANG II generation during acute UUO, ipsilateral and contralateral renal blood flow and renal secretion rate of ANG II were determined in pigs during continuous infusion of an angiotensin I converting enzyme (ACE) inhibitor. Pigs were operatively equipped with electromagnetic flow probes and catheters in the renal veins and aorta. Intravenous administration of the ACE inhibitor SQ 14 225 (captopril), 1 mg/kg per hour, resulted in a significant increase in renal blood flow in the contralateral kidney from 340±28 ml/min to 435±36 ml/min (P<0.01), whereas renal blood flow in the ipsilateral kidney was significantly reduced from 388±23 ml/min to 248±24 ml/min, similar to the reduction in controls. Captopril reduced mean aortic blood pressure, renal vascular resistance consistently on both sides, and plasma concentrations of ANG II and aldosterone from all sample sites. Renal secretion rate of ANG II showed a clear tendency to be reduced from the ipsilateral kidney. The results suggest that in UUO a compensatory increase in renal blood flow may be inhibited in part due to an enhanced secretion of ANG II in the ipsilateral kidney. However, a captopril-mediated inhibition of bradykinin breadown may also explain some of the observed changes.     

The Effects of Intraoperative Fenoldopam on Renal Blood Flow and Tubular Function following Suprarenal Aortic Cross-clamping

This study evaluated the effect of fenoldopam, a selective dopamine (DA1) agonist, on renal blood flow and renal tubular function following renal ischemia induced by suprarenal aortic cross-clamping. Twenty anesthetized research pigs received either fenoldopam (10 µg/kg/min; n = 10) or saline (n = 10) beginning 20 min before suprarenal aortic cross-clamping and continuing for 20 min after clamp release, for a total infusion time of 160 min (120-min cross-clamp). Recordings of renal blood flow, mean arterial pressure, and heart rate were taken at baseline, during cross-clamping, and immediately postclamp. Ischemic renal injury was evaluated by serum creatinine and by histologic grading of acute tubular necrosis. Treatment with fenoldopam increased renal blood flow in comparison to that in the control group (p = 0.03). The mean creatinine increase from baseline at 6 hr and 18 hr after cross-clamp removal for the fenoldopam-treated group was significantly less than that in the control group (p < 0.001). On histologic evaluation, the mean score for the degree of tubular necrosis was significantly higher in the control group (p = 0.02), indicating less derangement of tubular morphology in the fenoldopam group. This study demonstrated that the intraoperative use of a continuous infusion of fenoldopam during suprarenal aortic cross-clamping results in increased renal blood flow, less postoperative rise in creatinine, and better preservation of tubular histology in the pig model. Presented at the Thirteenth Annual Winter Meeting of the Peripheral Vascular Surgery Society, Snowmass, CO, January 31–February 2, 2003. The opinions or assertions contained herein are the private views of the authors and do not purport to reflect the position of the Department of the Air Force or the Department of Defense.     

A comparison of traditional open,minimal-incision donor nephrectomy and laparoscopic donor nephrectomy

Laparoscopic donor nephrectomy (LDN) and minimal-incision donor nephrectomy (MILD) are less invasive procedures than the traditional open donor nephrectomy approach (ODN). This study compares donor and recipient outcome following those three different procedures. Sixty consecutive donor nephrectomies were studied (n=20 in each group). Intra-operative variables, analgesic requirements, donor recovery, donor/recipient complications and allograft function were recorded prospectively. Operating and first warm ischaemia times were longer for LDN than for ODN and MILD (232±35 vs 121±24 vs 147±27 min, P<0.001; 4±1 vs 2±2 vs 2±1 min, P<0.01). Postoperative morphine requirements were significantly higher after ODN than after MILD and LDN (182±113 vs 86±48 vs 71±45 mg; P<0.0001). There was no episode of delayed graft function in this study. Donors returned to work quicker after LDN than after ODN and MILD (6±2 vs 11±5 vs 10±7; P=0.055). Donor and recipient complication rates and recipient allograft function were comparable. We concluded that MILD and LDN reduce postoperative pain and allow a faster recovery without compromising recipient outcome.     

Intraoperative fluid management in laparoscopic live-donor nephrectomy<Emphasis Type="SmallCaps">: C</Emphasis>hallenging the dogma

Background Patients undergoing laparoscopic live donor nephrectomy (LLDN) commonly receive large amounts of fluid intraoperatively to counter the negative effects of pneumoperitoneum on renal function. Our aim is to demonstrate that a low-volume fluid management strategy does not adversely affect donor or recipient outcomes. Methods Fifty-two patients underwent LLDN between December 2000 and January 2004. Data were collected in prospective databases, and augmented with retrospective medical record review. Donors were divided into two groups: the fluid-load group (n=24) received >10 ml/kg/h of intravenous crystalloids intraoperatively, while the fluid-restriction group (n=28) received <10m/kg/h. Results Donors in the fluid-restriction group had a lower intraoperative urine output. There were no differences in postoperative creatinine levels (117.5 μmol/L vs 121.5 μmol/L,p=0.8) or complications (4.2% vs 7.1%,p=0.9). In the recipients, there were no differences in postoperative creatinine levels up to 12 months, incidence of delayed graft function (18% vs 10%,p=0.7) or acute rejection (9% vs 5%,p=1.0) between groups. Conclusion Lower volume fluid management strategies in LLDN do not appear to worsen recipient outcomes nor are they detrimental to the donors. Online publication: 13 October 2004 Presented at the annual meeting of the Society of American Gastro-intestinal Endoscopic Surgeons (SAGES), Denver, CO, USA, March 2004     

Renal function remains after unilateral total and contralateral partial nephrectomy: an experimental study in pigs using 99mTc-DTPA

Twelve nephrectomies (NEs) were performed in 12 pigs (11–17 kg). Total NE was performed on the left side and partial NE on the right side (lower third of the kidney), thus two-thirds of the total kidney volume was removed. Renal function was studied with ^99mTc-diethylenetriaminepentaacetic acid (DTPA) renography and serum urea and creatinine levels preoperatively, and 1 and 2 weeks postoperatively. The pigs were imaged in each session for 30 min by collecting 10-s frames from a posteroanterior (PA) view of an anaesthesized animal. The injected activity was 37 MBq. Serial blood samples were taken from the subclavian vein at 0, 1, 2, 3, 5, 15, 25, 40, 60 and 120 min (six animals) after ^99mTc-DTPA injection. The DTPA disappearance rate (DDR) was determined from these samples and in other cases (six animals) a blood sample at 20 min was used. The DDR was also determined from the dynamic gamma imaging data: Regions of interest (ROI) were upper body, spleen, heart and kidneys. The ROI analysis correlated well with the blood sampling data (r=0.97, P<0.0001). The reference values for pig DDRs were 0.99±0.08%/min. These values were 0.71±0.08%/min at 1 week postoperatively and 0.63±0.08%/min at 2 weeks. DTPA clearance rates were preoperatively 0.53±0.06 ml/s; at 1 week postoperatively 0.41±0.06 ml/s; and at 2 weeks 0.35±0.06 ml/s. There were no significant differences pre- and postoperatively in creatinine and urea concentrations. The DTPA clearance (ml/s) and disappearance rates (%/min) when determined per kidney area (cm²) increased significantly (P<0.001 at both 1 and 2 weeks); in 11 of 12 animals the function of the resected right kidney was higher than the split function of the whole right kidney preoperatively. Unilateral nephrectomy initiates a functional adaptation or a growth response in the contralateral kidney to compensate for the loss of a renal mass. These data also indicate that two-thirds of the kidney volume in young pigs can be removed without danger.     

Optimization of cardiac preload during laparoscopic donor nephrectomy: A preliminary study of central venous pressure versus esophageal doppler monitoring

Background: While the popularity of laparoscopic donor nephrectomy (LDN) has increased, concern persists about the potential deleterious effects of pneumoperitoneum on renal function. Thus, preload optimization with vigorous intravenous hydration has been recommended. The purpose of this study was to compare central venous pressure (CVP) monitoring with a noninvasive measure of cardiac preload (esophageal Doppler) during LDN. Methods: Thirteen patients were studied. Following induction of general anesthesia, a Doppler probe was inserted in the lower third of the esophagus to measure flow time corrected for heart rate (FTc), which is an index of preload. In 10 patients, a catheter was placed in the right internal jugular vein and CVP measured. CVP and FTc were measured at baseline in the supine and right lateral decubitus positions, then 15 and 60 min after the establishment of CO₂ pneumoperitoneum (12–15 mmHg). IV fluids were increased if the FTc fell below 300 msec. Results are expressed as means (±SD). Data were analyzed using repeated measures ANOVA. Results: Lateral positioning and pneumoperitoneum significantly increased CVP from baseline (p < 0.01), while the FTc did not change (p = 0.57). After 60 min of pneumoperitoneum, the FTc was <300 msec in only one patient. Conclusion: CVP is not an accurate guide for administration of IV fluids during LDN. Esophageal Doppler monitoring can be used to noninvasively follow changes in preload during LDN and is worthy of further study. Presented at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons (SAGES), Los Angeles, CA, USA, March 2003 Financial Disclosure. This work was supported by an unrestricted educational grant from Tyco Healthcare.     

Protective effect of a platelet-activating factor antagonist (WEB-2086) in postischemic renal failure

The purpose of this study was to evaluate the renoprotective effect of a specific platelet-activating factor antagonist (WEB-2086) in an experimental model of normothermic renal ischemia. Twenty New Zealand white rabbits were studied for 2 days before and 24 hours after a 60-minute period of renal ischemia induced by bilateral clamping of the renal arteries. The animals were divided into two groups: a control group (group A; n=10) and a treated group (group B; n=10). In group A the urinary flow rate decreased significantly (from 0.098±0.008 ml/min to 0.029±0.005 ml/min) (p<0.001) and there was a significant reduction in creatinine clearance (from 11.4±1.2 ml/min to 3.4±1.1 ml/min) (p<0.001). In group B no significant changes were observed, although the urinary flow rate increased even in the postischemic period (from 0.09±0.008 ml/min to 0.11±0.02 ml/min). Microcirculatory cortical flow showed a postischemic reduction in both groups, although it was most significant in the control group (group A=43.7%, group B=71.5%;p<0.001). Histologic study showed mild damage with patchy tubular necrosis in both groups, although this injury was less severe in the treated group. The results suggest that the preoperative administration of WEB-2086 produces a potent diuretic effect with significant attenuation of postischemic acute renal failure.Presented at the Seventeenth World Congress of the International Union of Angiology, London, England, April 3–7, 1995 (IUA Prize).Supported by a grant from the National Institutes of Health (INS) (FIS 95/0837), Madrid, Spain.     

Can right‐sided hand‐assisted retroperitoneoscopic donor nephrectomy be advocated above standard laparoscopic donor nephrectomy: a randomized pilot study

Endoscopic techniques have contributed to early recovery and increased quality of life (QOL) of live kidney donors. However, laparoscopic donor nephrectomy (LDN) may have its limitations, and hand‐assisted retroperitoneoscopic donor nephrectomy (HARP) has been introduced, mainly as a potentially safer alternative. In a randomized fashion, we explored the feasibility and potential benefits of HARP for right‐sided donor nephrectomy in a referral center with longstanding expertise on the standard laparoscopic approach. Forty donors were randomly assigned to either LDN or HARP. Primary outcome was operating time, and secondary outcomes included QOL, complications, pain, morphine requirement, blood loss, warm ischemia time, and hospital stay. Follow‐up time was 1 year. Skin‐to‐skin time did not significantly differ between both groups (162 vs. 158 min, P = 0.98). As compared to LDN, HARP resulted in a shorter warm ischemia time (2.8 vs. 3.9 min, P < 0.001) and increased blood loss (187 vs. 50 ml, P < 0.001). QOL, complication rate, pain, or hospital stay was not significantly different between the groups. Right‐sided HARP is feasible but does not confer clear benefits over standard right‐sided LDN yet. Further studies should explore the value of HARP in difficult cases such as the obese donor and the value of HARP for transplantation centers starting a live kidney donation program (Dutch Trial Register number: NTR3096). Nevertheless, HARP is a valuable addition to the surgical armamentarium in live donor surgery.     

Serum beta 2 microglobulin levels in patients with renal cell carcinoma

Summary Serum B₂m concentrations were evaluated preoperatively in 40 patients with renal cell carcinoma and normal renal function, as assessed by serum creatinine <1.4 mg/dl, and compared with those of 23 age-matched controls. Mean value ± SD was 3,088±966 ng/ml for renal cancer patients, while controls had a value of 1,800±240 ng/ml. Statistical analysis, performed by Student t test, revealed a very high degree of significance (p<0.0005). No statistically significant differences were found between groups of patients classified according to tumor stage and cell type. Seventy percent of renal cell carcinoma cases had preoperatively elevated serum levels of B₂m.     

Benefit of theophylline administration in tacrolimus-induced nephrotoxicity in rats

Tacrolimus (TAC), a widely used nephrotoxic calcineurin inhibitor, is associated with renal vasoconstriction possibly through adenosine receptor activation. Theophylline (THEO), an adenosine receptor inhibitor, protects against the nephrotoxicity of drugs associated with renal vasoconstriction. We hypothesized that coadministration of low dose THEO in rats would prevent TAC-induced nephrotoxicity. Sprague-Dawley rats pair-fed a low-sodium diet were randomized into three groups (n=10/group): the control (CONTROL) group received the vehicle for both medications; the TAC group received TAC 6 mg/kg/day and vehicle; and the TAC+THEO group received TAC and THEO 17 mg/kg/day. On day 21, a timed urine collection was obtained for creatinine clearance. On day 22, serum creatinine, THEO and whole blood TAC concentrations were determined. One kidney was removed for formalin fixation and histological assessment. In the TAC group, serum creatinine increased while creatinine clearance decreased compared to CONTROL (0.3±0.0 vs. 0.4±0.0 mg/dl and 0.53±0.06 vs. 0.34±0.04 ml/min/100 g body weight respectively, p<0.05), while TAC+THEO did not differ from control. There were no significant differences in renal histology. Concurrent administration of low-dose THEO prevented the TAC-induced decline in renal function, consistent with a role for adenosine in TAC-induced nephrotoxicity.     

Kidney transplantation from non-heart-beating donors after oxygenated low-flow machine perfusion preservation with histidine–tryptophan–ketoglutarate solution

The aim of this study was to determine the potential benefit of aerobic machine preservation (MP) with non-colloidal histidine–tryptophan–ketoglutarate (HTK) solution compared with MP with Belzer machine perfusion solution (MPS) and standard cold storage, after marginal kidneys had been obtained from non-heart-beating donors. Cardiac arrest was electrically induced in anaesthetized German landrace pigs (20–25 kg bw). Their kidneys were harvested 40 min thereafter, flushed with HTK by gravity of 100 cm H₂O via the renal artery and then stored in HTK for 18 h at 4°C. Other organs were subjected to oxygenated (pO₂>500 mmHg) hypothermic pulsatile low-flow machine perfusion with HTK or MP with Belzer MPS at P_max=40 mmHg, yielding transrenal flow values of 0.2–0.3 ml/min per g with HTK and approximately twice that amount with Belzer MPS. A well-preserved vascular endothelium and intact tubular epithelium were documented by electron microscopy at the end of perfusion preservation in both solutions as well as after cold storage. Concentrations of ATP (in micromoles per gramme) in tissue homogenates at the end of perfusion preservation with HTK were 1.18±0.12 vs 0.16±0.02 (P<0.05) after simple cold storage and 2.43±0.23 after perfusion with Belzer MPS, thus documenting a relevant effect of low-flow perfusion on tissue oxygenation. Viability of the grafts was followed for 1 week after heterotopic transplantation and bilateral nephrectomy in the recipient pigs. Machine perfusion with HTK significantly improved cortical microcirculation upon early reperfusion in vivo, as well as maximal serum levels of urea and creatinine, compared to recipients receiving cold-stored grafts. No differences could be found between MP with HTK or Belzer MPS. In conclusion, provision of oxygen during storage is possible by low-flow perfusion with HTK as with Belzer MPS and apparently improves graft viability after transplantation.     

Palliation for pancreatic cancer

Background: Although laparoscopy reveals undetected metastases in many patients with pancreatic cancer, most surgeons have chosen to proceed directly with laparotomy in an attempt at resection or for palliation of biliary and gastric outlet obstruction. In an effort to overcome this limitation, this study attempted to determine the feasibility of laparoscopic cholecystojejunostomy and gastrojejunostomy. Methods: Under general anesthesia, seven pigs underwent laparoscopic cholecystojejunostomy and gastrojejunostomy using either a hand-sutured or the stapled/sutured technique. Results: Mean operating time was less with the stapled/sutured vs hand-sutured technique (150±21 vs 230±13 min, P<0.05). All animals recovered completely and there was no change in their weight or liver function tests as a result of the procedure. At sacrifice, all anastomoses were patent, although some were significantly narrowed in these unobstructed animals. Conclusions: These results suggest that simultaneous laparoscopic palliation of biliary and gastric outlet obstruction is feasible. We believe these results warrant further study in the clinical setting.Presented at the Society of American Gastrointestinal Endoscopic Surgeons (SAGES), April, 1994, Nashville, TN, USA     

Transmyocardial laser – revascularization: experimental studies on prolonged acute regional ischemia

Objective: This experimental study in pigs was undertaken to answer the question whether TMLR after acute myocardial infarction may improve regional myocardial perfusion, left ventricular function and diminish myocardial necrosis in the area at risk. Methods: Thirty open-chest anesthetized pigs were observed for 6 h, six pigs served as controls. In 24 pigs, occlusion of the left anterior descending artery (LAD) beyond the first diagonal branch was performed: seven pigs had LAD occlusion only (ischemia group), and 17 pigs were treated by TMLR (using a CO₂-laser, energy: 40 J) prior to coronary occlusion; nine pigs received one laser channel (1 mm diameter) per cm² (laser group 1) and eight pigs two channels per cm² in the LAD territory (laser group 2). Regional myocardial blood flow by microspheres, function (franc starling curves), histochemical assessment (triphenyl tetrazolium chloride, TTC and histology), were performed. Results: The lased pigs were less prone to ventricular fibrillation (laser group 2, 38%; laser group 1, 56%; ischemic group, 100%; P<0.05), and showed a significant smaller area of necrosis (TTC) in the area at risk (laser group 1, 23%; laser group 2, 14%; vs. ischemia group, 31%; P<0.01). There was no significant difference between laser-treated and ischemia hearts regarding the amount of blood flow into the infarcted LAD region and the maximal left ventricular stroke work index after 6 h (P=n.s). Regional myocardial blood flow: ischemia group, 4±5 ml/100 g/min; laser group 1, 3±10 ml/100 g/min, and laser group 2, 2±10 ml/100 g/min; maximal left ventricular stroke work index: ischemia group, 1.8 mJ/g; laser group 1, 2.1 mJ/g and laser group 2, 2.1 mJ/g. Conclusions: This model of acute regional ischemia demonstrates that CO₂-laser revascularization diminish significantly the incidence of ventricular fibrillation and necrosis in the area at risk, and does not change regional myocardial perfusion and global left ventricular function. This experiment indicates that TMLR may be an alternative in treating advanced ischemic heart disease.     

Effect of indomethacin on renal function in anaesthetized dogs

The inhibitory action of indomethacin administered as a single-dose injection (4 mg/kg) was examined under general anaesthesia in dogs, moderate volume expansion having been induced with physiological saline infusion. At 20 to 30 min after the administration of indomethacin, excretion of Na and water showed a fall of the same extent, GFR remaining stable and the effective plasma flow (C_PAH) declining. RBF estimated by the⁸⁶Rb method decreased from 411±96 ml/min/100 g to 292±±53 ml/min/100 g (p<0.01). This fall was coupled with an intrarenal redistribution of blood flow. While the cortical fraction of renal blood flow increased from 79% to 83.9% (p<0.001), its outer medullary fraction decreased from 17% to 13.2% (p<0.001) and its inner medullary fraction from 4.0% to 2.8% (p<0.05). The renal, primarily the medullary, vasculature is assumed on these grounds to be under the influence of a continuous secretion of prostaglandins which thus seem to be involved in the physiological control of intrarenal distribution of blood flow and of sodium and water excretion.     

Renal blood flow and pelvic pressure after 4 weeks of total upper urinary tract obstruction in the pig

Summary In 8 female pigs complete unilateral ureteral obstruction was investigated over a 4 weeks period. The pigs were monitored with intrapelvic pressure measurements and by 131-I-hippuran scintigraphy twice a week; one group without and one with TxA₂ blocking, UK-38,485 [3-(1H-imidazol-1-yl-methyl)-2methyl-1H-indol-1-propanoic acid], which is a well-known selective thromboxane synthetase inhibitor. During the course of obstruction there was an ipsilateral linear reduction of split function to background level and a net reduction in total hippuran clearance in both groups. On the obstructed side there was a linear reduction of hippuran clearance from 116±26 ml/min to 11±3 ml/min during the first 2 weeks of obstruction. The TxA₂ synthetase inhibitor, 5 mg/kg reduced se-TxB₂ to almost zero for at least one hour after i.v. administration. One week after obstruction the pelvic pressure was 45±5 cm H₂O administration of the TxA₂ synthetase inhibitor. The pelvic pressure remained elevated throughout the period of observation. The study confirmed earlier work which showed that total ureteral obstruction caused complete cessation of kidney function within a few weeks, but contradicts previous studies because there was no increase in renal blood flow after thromboxane blockade. These differences may be explained by several mechanisms. The continuing increase in pelvic pressure suggested that it was not only a preglomerular vasoconstriction which was responsible for the renal flow reduction, but that there was also a postglomerular vasoconstriction.     

Natural history and etiology of hyperuricemia following pediatric renal transplantation

A retrospective review was conducted to determine the incidence, etiology, natural history and complications of hyperuricemia after pediatric renal transplantation. Of 81 active transplant recipients aged 10.1±4.8 (mean±SD) years being followed by St. Christoper's Hospital for Children, 57 (70%) were males and 59 (73%) Caucasian. Their immunosuppression consisted of azathioprine, cyclosporine A and prednisone. Mean serum uric acid concentrations peaked at 6 months post transplantation (6.2±2.6 mg/dl), when 39% of the patients had hyperuricemia and 60% were receiving diuretics, and decreased thereafter. At 30 months, 23% of the patients had hyperuricemia and 17% required diuretics. When we compared 42 normouricemic (group A) with 24 hyperuricemic (group B) patients at 18 months post transplantation, we found that patients in group B were older (11.6±4.2 vs. 8.6±5.2 years,P=0.01), had worse renal function (77±25 vs. 96±36 ml/min per 1.73 m²,P=0.03) and required diuretics more frequently (63% vs. 21%,P=0.001), but had identical blood levels of cyclosporine A (82±28 vs. 84±35 ng/ml,P=0.78). A family history of gout did not affect the prevalence of hyperuricemia after transplantation. Asymptomatic hyperuricemia is common following pediatric renal transplantation and is more likely attributable to reduced renal function and diuretic therapy than to the known hyperuricemic effect of cyclosporine A. Of these variables, only diuretic therapy is readily controllable and should be closely regulated following pediatric renal transplantation.     

Renal function in children with idiopathic hypercalciuria

Abnormalities in renal tubular function have been reported in adult patients with idiopathic renal hypercalciuria. To determine if such abnormalities are present early in the natural history of renal hypercalciuria, we evaluated renal tubular function in ten children with idiopathic renal hypercalciuria, aged 5–17 years. Seven of the children presented with urolithiasis and three with hematuria. Urinary calcium excretion ranged from 4 to 9 mg/kg per day, (5.2±0.5, mean ± SEM) with a mean fasting urinary calcium to creatinine ratio of 0.31±0.03. Studies described in this report were performed after 1 week of ingesting a diet containing 1,000 mg calcium, 3,000 mg sodium, and 100 mg purine. Clearance of creatinine ranged from 84 to 159 ml/min per 1.73 m². Tm phosphate (mg/100 ml GFR) was normal in each child (mean 4.66±0.06 mg/100 ml GFR). Fractional excretion of uric acid, sodium and beta-2-microglobulin were also normal in each child. Serum bicarbonate concentrations ranged from 21.5 to 27 mEq/l with a mean of 24.4±0.5 mEq/l and all patients lowered urinary pH to <5.5. Hypotonic diuresis demonstrated normal free water clearance with a mean of 12.8 ml/min per 100 ml C_in. Distal sodium delivery and fractional distal sodium reabsorption were normal with a mean of 13.6±1.2% and 92.7±0.5%, respectively. Water deprivation studies demonstrated a range of maximum urinary osmolality from 711 to 1,020 mosmol/kg H₂O with a mean of 864±34 mosmol/kg H₂O. Seven healthy children, ingesting an identical study diet, concentrated their urine to a mean of 1,059±31 mosmol/kg h₂O. Thus, only a partial defect in urinary concentrating ability was identified in these studies of renal function in children with renal hypercalciuria. Our data demonstrate that idiopathic renal hypercalciuria is not the result of a generalized renal tubulopathy nor is it the result of renal tubular acidosis in these children. These findings suggest that renal tubular dysfunction in adult patients with hypercalciuria may be secondary to repeated episodes of urolithiasis or to life-long hypercalciuria.This project was supported by a Clinical Associate Physician Award (FBS) no. RR00211-19 from the General Clinical Research Center